The midfielder picked up the knock in training last week after starting the previous four games.
Ledson will be needed for the engine room at the KCOM Stadium as Ben Pearson is suspended for reaching the five bookings mark.
North End manager Alex Neil told the Post: “Ryan was disappointed to miss out because he wanted to be involved.
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“He has got a high ankle sprain and it would have been quite a risk.
“Ryan wanted to strap it up and be on the bench.
“But my worry was if Ben Pearson, for instance, had been forced to come off after five minutes, I’m not sure Ryan could have lasted 85 minutes at full tilt.
“It was a game where we couldn’t risk anyone being half-injured if you like.
“The other week I had done the same with Paul Gallagher – he’d has an issue with his back so I just left him out for a game to get him right.
“We did that with Ryan and he will be back for the next one.”
Daniel Johnson came into the starting XI against Wigan to replace Ledson.
That change would have been made notwithstanding Ledson’s injury, with Johnson having taken over from him at half-time at Aston Villa.
DJ was to prompt Preston’s comeback and he performed well again in the 4-0 victory over Wigan.
Pearson’s fifth yellow card of the campaign came in the first-half when he caught Nick Powell from behind.
Said Neil: “That was Ben’s fifth booking and was one which he probably had to take for the team to stop a breakaway.
“It’s the ones for the mouth which he has to sort out.”
Keeping Ledson company on the sidelines on Saturday was Paul Huntington.
The centre-back was ruled out with an injury he suffered at Villa.
Neil said: “Hunts had a bit of a groin problem.
“He felt something in the second half at Aston Villa and wasn’t ready for Saturday.”
After taking four points from the last two matches, PNE can now take a breather in the international break.
Neil will use the break to mix work on the training pitch with a few days rest.
They resume at Hull a week on Saturday before having a Deepdale double header with Brentford and Rotherham.